Search

A condition-based maintenance optimization approach is developed for the road-cracking problem in order to derive optimal maintenance policies that minimize a total discounted maintenance cost. The approach is based on a Markov decision process that takes into account multiple actions with varying effects on future road performance. Maintaining the road consists of adding a new asphalt layer; however, as resurfacing actions are constrained by a maximum total road thickness, the maintenance decision is not only how thick a layer to apply, but also how much old road to remove. Each combination of these actions leads to different maintenance costs and different future degradation behaviours. The road state is modelled by a dependent bivariate deterioration variable (the longitudinal cracking percentage and the deterioration growth rate), for taking these different changes in the cracking patterns into account. Moreover, the sensitivity to cracking for existing roads can be reduced with the addition of new layers, and thus actions that can lead to states better than good-as-new have to be considered. A numerical analysis is provided to illustrate the benefits of the introduction of the deterioration speed in the decision framework, as well as the belief that initially building a road to its maximum thickness is not optimal. The trade-offs in the design decisions and the exploitation/maintenance costs are also explored.

It has long been puzzling regarding the physical origin of the thermally induced red-shift of Raman optical phonons in group III nitride crystals despite some possible mechanisms such as phonon decay, thermal expansion, interfacial effects, or their combinations. Here we show that an extension of the recent approach Sun, C. Q.; Pan, L. K.; Li, C. M.; Li, S. Phys. Rev.B2005, 72, 134301 to the functional dependence of the frequency of Raman optical modes on the atomic bonding identities (bond length, bond strength, and atomic coordination numbers) to the temperature domain has enabled us to gain a simple solution with improved understanding of the thermally induced red-shift of Raman optical phonons. Reproduction of the measured temperature dependence of the Raman shift of AlN, GaN, and InN reveals that the thermally driven red-shift arises simply from bond vibration and bond expansion, together with derived information about the modecohesive energy.

Epidermal growth factor (EGF) stimulates the homodimerization of EGF receptor (EGFR) and the heterodimerization of EGFR and ErbB2. The EGFR homodimers are quickly endocytosed after EGF stimulation as a means of down-regulation. However, the results from experiments on the ability of ErbB2 to undergo ligand-induced endocytosis are very controversial. It is unclear how the EGFR-ErbB2 heterodimers might behave. In this research, we showed by subcellular fractionation, immunoprecipitation, Western blotting, indirect immunofluorescence, and microinjection that, in the four breast cancer cell lines MDA453, SKBR3, BT474, and BT20, the EGFR-ErbB2 heterodimerization levels were positively correlated with the ratio of ErbB2/EGFR expression levels. ErbB2 was not endocytosed in response to EGF stimulation. Moreover, in MDA453, SKBR3, and BT474 cells, which have very high levels of EGFR-ErbB2 heterodimerization, EGF-induced EGFR endocytosis was greatly inhibited compared with that in BT20 cells, which have a very low level of EGFR-ErbB2 heterodimerization. Microinjection of an ErbB2 expression plasmid into BT20 cells significantly inhibited EGF-stimulated EGFR endocytosis. Coexpression of ErbB2 with EGFR in 293T cells also significantly inhibited EGF-stimulated EGFR endocytosis. EGF did not stimulate the endocytosis of ectopically expressed ErbB2 in BT20 and 293T cells. These results indicate that ErbB2 and the EGFR-ErbB2 heterodimers are impaired in EGF-induced endocytosis. Moreover, when expressed in BT20 cells by microinjection, a chimeric receptor composed of the ErbB2 extracellular domain and the EGFR intracellular domain underwent normal endocytosis in response to EGF, and this chimera did not block EGF-induced EGFR endocytosis. Thus, the endocytosis deficiency of ErbB2 is due to the sequence of its intracellular domain.

Summary A prospective observational study of the pathophysiology of sodium and water disorders in patients with pituitary region tumours after surgical excision was carried out in 20 patients. Serial pre-operative and post-operative fluid and sodium balance, plasma and urine elctrolyte biochemistry and their derived parameters, and circulating hormones associated with fluid balance, atrial natriureic peptide (ANP) and antidiuretic hormone (ADH) were documented to correlate with the patients' clinical conditions. Ten out of these twenty cases developed diabetes insipidus (DI) requiring ADH replacement therapy, although in the majority (6 cases), this way only a transient event. Of the nine patients who developed hyponatraemia, six had symptoms such as impaired consciousness and convulsions. Four patients developed alternating hypoatraemia and hypernatraemia, which constituted a difficult group, where appropriate sodium and fluid management, and ADH replacement therapy were based upon twice daily plasma and urine biochemistry and their derived parameters. Whilst DI in this group of patients was the result of a low circulating ADH level, hyponatraemia was not associated with an exaggerated ADH activity (6.0 ± 2.3 vs 7.4 ± 2.3 pmol/ml, mean ± SEM). Rather, hyponatraemia was strongly associated with an elevated circulating ANP concentration (82.4±10.5 vs 30.0 ±3.1 pmol/ml, mean ± SEM, p < 0.001), resulting in salt wasting and hypovolaemia.

A histological assessment has been made of both time- and dose-related changes in the choroid plexus after the local irradiation of the rat brain with single doses of 17.5–25 Gy of X rays. These investigations involved the serial killing of animals 1–52 weeks after irradiation and the quantitative and semiquantitative evaluation of histological sections. Counts of the relative number of cells in the choroid plexus of the lateral ventricles showed an atrophy of the epithelial layer after 13 weeks. However, this was not as marked as the reduction in the number of endothelial cells in the wall of blood vessels. Moreover, the epithelium had recovered by 39 weeks after irradiation, while the dose-related depletion in endothelial cells tended to be progressive. A highly correlated group of changes in the vascular-connective tissue was used to produce a numerical “factor”. This represented a combined score of radiation damage which was both time- and dose-related. These data suggest that, as an expression of late radiation damage to the choroid plexus, the effect on the endothelium was more important than that to the epithelial cells.

Following the local irradiation of the rat brain with single doses of 17.5–25 Gy of X rays, necrosis of the white matter was seen after a latent interval of > 26 weeks. At 39 weeks and 52 weeks after irradiation the incidence of necrosis was doserelated. The doses associated with a 50% incidence of necrosis in the white matter (ED50) at these times were 23.45 ± 0.49 and 20.98 ± 0.91 Gy, respectively. At both these times the incidence of necrosis was higher in the fimbria than in the capsula interna and the corpus callosum. This reflects a variation in the latency time for the appearance of necrosis. Necrosis occurs earlier in the fimbria. In the corpus callosum and the capsula interna the latency times for the appearance of necrosis were also dosedependent. In the latent period prior to the onset of necrosis of the fimbria, a number of dose-related changes were seen in the vasculature and the associated astroglial cells. These changes, which included blood vessel dilation, blood vessel wall thickening, endothelial cell nuclear enlargement and the hypertrophy of perivascular astrocytes, were highly correlated and when combined appeared to represent a “unit of tissue injury”. The incidence and severity of this “unit of tissue injury” apparently increased with time after irradiation until necrosis ensued. These dose-related vascular/glial changes were preceded by a reduction in the endothelial cell and vascular density. No early changes were seen in the number of glial parenchymal cells.

It has been proposed that one of metronidazole's partially reduced intermediates interacts either with DNA to exert a bactericidal effect or with water to form acetamide. To test this hypothesis we have examined the effect of metronidazole on several mutants of Escherichia coli that are defective in DNA repair. UV-susceptible RecA- and UvrB- point mutants have an increased susceptibility to metronidazole as manifested by both a decreased minimal inhibitory concentration and a greater bactericidal response to metronidazole in resting cultures. By these criteria, however, we find that UvrB- deletion mutants, which lack the ability to reduce nitrate and chlorate, are no more susceptible to metronidazole than is the wild type. We find, however, that these deletion mutants also lack the ability to reduce metronidazole and thus possibly to form its reactive species. When metronidazole's bactericidal effect is expressed in terms of the concurrent accumulation of acetamide derived from metronidazole, then all RecA- and UvrB- mutants are killed more efficiently than their wild types. The data are consistent, therefore, with metronidazole's lethal effect being mediated by a partially reduced intermediate on the metabolic pathway between metronidazole and acetamide. Defects in other aspects of the DNA repair system do not confer this increased susceptibility to the proposed intermediate. A Tag- mutant, for example, which is defective in 3-methyl-adenine-DNA glycosylase, does not have this increased susceptibility to the presumed precursor of acetamide. Thus, these results provide further support for the hypothesis that the bactericidal effect of metronidazole is mediated by a partially reduced intermediate in the metabolic conversion of metronidazole to acetamide and suggest that this intermediate interacts with DNA to produce a lesion similar to that caused by UV light.